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Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors. Nat Commun 2015 Jan 13;6:6077

Date

01/15/2015

Pubmed ID

25584517

Pubmed Central ID

PMC4364406

DOI

10.1038/ncomms7077

Scopus ID

2-s2.0-84923079683   79 Citations

Abstract

Insect odorant receptors (ORs) comprise an enormous protein family that translates environmental chemical signals into neuronal electrical activity. These heptahelical receptors are proposed to function as ligand-gated ion channels and/or to act metabotropically as G protein-coupled receptors (GPCRs). Resolving their signalling mechanism has been hampered by the lack of tertiary structural information and primary sequence similarity to other proteins. We use amino acid evolutionary covariation across these ORs to define restraints on structural proximity of residue pairs, which permit de novo generation of three-dimensional models. The validity of our analysis is supported by the location of functionally important residues in highly constrained regions of the protein. Importantly, insect OR models exhibit a distinct transmembrane domain packing arrangement to that of canonical GPCRs, establishing the structural unrelatedness of these receptor families. The evolutionary couplings and models predict odour binding and ion conduction domains, and provide a template for rationale structure-activity dissection.

Author List

Hopf TA, Morinaga S, Ihara S, Touhara K, Marks DS, Benton R

Author

David S. Marks MD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acids
Animals
Evolution, Molecular
Insecta
Receptors, Odorant
Xenopus